Diffusion-Weighted MRI for Breast Cancer Screening in Women With a Personal History of Breast Cancer

Breast Cancer Clinical Trial

Official title:

Comparison of Diffusion-Weighted MRI and Mammography Alone or Combined Mammography and Ultrasonography for Screening Women With a Personal History of Breast Cancer (DIMRISC-2 Study)

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04619186
• Other study ID #: Breast Cancer Screening
• Status: Suspended
• Start date: December 30, 2024
• Est. completion date: December 30, 2026

Study information

• Verified date: May 2024
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Women with personal history of breast cancer (PHBC) are at risk of developing second breast cancers in the conserved and contralateral breast. Because early detection of second breast cancers at the asymptomatic phase can improve relative survival by 17-28%, guidelines recommend annual mammography screening in women with PHBC. However, lower sensitivity and higher interval cancer rates are observed in women with a PHBC compared with women without, especially in women 50 years or younger and those with dense breasts. In a multicenter comparison study of 754 women, MRI screening detected 3.8 additional cancers and ultrasonography detected 2.4 additional cancers, and increased sensitivity over mammography alone. However, the use of breast MRI is limited not only by high costs and long examination time but also by high false-positive findings. In addition, the use of intravenous gadolinium-based contrast agent is contraindicated in women with renal impairment or contrast material allergy contrast. Supplemental ultrasonography in patients with PHBC reports lower sensitivity with high interval cancer rate. Thus, there is a need to develop a more safe, accurate, and cost-effective supplemental imaging modality for screening in women with PHBC. Diffusion-weighted (DW) MRI is an unenhanced fast, functional modality that measures the movement of water molecules to create tissue contrast. Breast malignancies exhibit hindered diffusion and appear hyperintense on DW MRI with low apparent diffusion coefficient (ADC) compared to normal surrounding tissue. Multiple studies have shown that the use of DW MRI can significantly reduce the false positives and unnecessary benign biopsy of breast MRI. Several studies have shown that DW MRI has a potential to detect mammography occult breast cancers with less false positives compared to ultrasonography. These observations have led to the consideration of utilizing DW MRI to screen women with PHBC. In Diffusion-weighted MRI for Breast Cancer Screening (DIMRISC-2) study, we hypothesized that the screening performance of high-resolution DW MRI at 3.0 T should be superior to mammography alone or combined mammography and ultrasonography in women with PHBC. In our institution, alternating conventional imaging and DW MRI screening is offered for patients who have undergone breast surgery and at increased risk of an interval second breast cancer.

Description:

• Primary objective: to compare the screening performance of DW MRI versus mammography alone or combined mammography and ultrasonography in women with PHBC.

• Secondary objective: to compare the tumor and patient characteristics detected by DW MRI and combined mammography and ultrasonography in women with PHBC.

• This is a prospective, single center, observational cohort study.

• A total of 1694 women will be enrolled in this study.

• Two latest 3.0 T MRI scanners with dedicated 16- or 18-channel bilateral breast coil are used for DW MRI. For DW MRI screening, the high-resolution echo-planar imaging sequence is designed to have an in-plane resolution of 1.3 x 1.3 mm and a slice thickness of 3 mm. Three b values of 0, 800, and 1200 sec/mm2 are used and ADC maps are generated based on the b=0 and 800 sec/mm2 DW MRI data. The DW MRI images are reconstructed into single summation images with maximum-intensity projections (MIPs) in the sagittal and axial planes. In addition, T1-weighted imaging sequence is also obtained with in-plane resolution of 1.0 x 1.0 mm and a slice thickness of 1 mm.

• All patients with PHBC undergo digital two-dimensional mammography and physician-performed whole-breast ultrasonography on the same day. DW MRI and conventional imaging (mammography and ultrasonography) are alternatively scheduled at 6-month intervals and the order has been randomized.

• Mammography alone, combined mammography and ultrasonography, and DW MRI will be interpreted independently according to the Breast Imaging Reporting and Data System (BI-RADS) and likelihood of malignancy (Score range, 0%-100%) by trained radiologists. DW MRI interpretation guidelines to be used in this study are based on both qualitative and quantitative assessments. Radiologists are required to successfully complete a training case series of 100 DW MR studies prior to interpreting the DW MRI.

• A negative examination result is defined as a final assessment BI-RADS category of 1, 2, 3 and a positive examination result is defined as a final assessment BI-RADS category of 4 or 5.

• Biopsies of DW MRI-detected lesions are performed under ultrasonography guidance whenever possible or with MR guidance if there is no correlative ultrasonography finding. Pathology of core or surgical biopsy and 1 year follow up is the reference standard.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 1694
• Est. completion date: December 30, 2026
• Est. primary completion date: December 30, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 25 Years and older

Eligibility

Inclusion Criteria:

1. Women over 25 years of age at the time of enrollment

2. Women who underwent breast conservation therapy or mastectomy and at increased risk of an interval second breast cancer (Age <50 at first cancer diagnosis; Breast density BI-RADS category 3 and 4; First degree family history; First breast cancer was an interval cancer or symptomatic presentation; First breast cancer was grade 2, 3 or ER and PR negative)

Exclusion Criteria:

1. Women with signs or symptoms of breast cancer

2. Women who had bilateral mastectomy

4. Women who had known metastatic disease 5. Pregnant or lactating women 6. Women with claustrophobia or metallic foreign body

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cancer detection rate (CDR)	Number of detected cancers (invasive cancer and DCIS) /1000 women	Baseline to up to 1 year
Secondary	Sensitivity	Number of positive examinations with a tissue diagnosis of cancer within 1 year/All examinations with tissue diagnosis of cancer within the same period	Baseline to up to 1 year
Secondary	Specificity	Number of negative examinations without tissue diagnosis of cancer within 1 year/All examinations without tissue diagnosis of cancer within the same period	Baseline to up to 1 year
Secondary	Recall rate	Percentage of women screened with recommendation for further imaging prior to next routine examination	Baseline to up to 1 year
Secondary	Positive predictive value (PPV)	PPV1: True positive/True positive + False positive; PPV2: Number of biopsy confirmed cancers/total number of recommendations for biopsy.; PPV3: Number of biopsy confirmed cancers/total number of biopsies performed	Baseline to up to 1 year
Secondary	Accuracy	Proportion of true positive results (both true positive and true negative) in the population; -The area under the (receiver operating characteristic) curve (AUC)	Baseline to up to 1 year
Secondary	Interval cancer rate	Breast cancer diagnosed within 1 year of a negative screening result because of clinical symptoms/1000 women	Baseline to up to 1 year
Secondary	Characteristics of detected cancers	Tumor size, type, grade, molecular subtype, and lymph node metastasis	Baseline to up to 1 year
Secondary	Characteristics of women with DW-MRI detected cancer	Age, menopausal status, breast density, family history	Baseline to up to 1 year